Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTO5D86M)

• DOT Name: Transmembrane channel-like protein 5 (TMC5)
• Gene Name: TMC5
• Related Disease:
  Alzheimer disease
  Prostate cancer
  Prostate carcinoma
  Lung adenocarcinoma
  Squamous cell carcinoma
• UniProt ID: TMC5_HUMAN
• Pfam ID: PF07810
• Sequence:
  MSAYYRNNWSEEDPDYPDYSGSQNRTQGYLKTQGYPDVPGPLNNPDYPGTRSNPYSVASR
  TRPDYPGSLAEPNYPRSLSNPDYSGTRSNAYSAASRTSPDHPTSLPEPDYSEFQSHPYHR
  ASSRQPDYPGSQRNPDFAGSSSSGNYAGSRTHPDHFGSLEPDYPGAQSNSDHPGPRANLN
  HPGSRKNLEHTSFRINPYADSLGKPDYPGADIQPNSPPFFGEPDYPSAEDNQNLPSTWRE
  PDYSDAENGHDYGSSETPKMTRGVLSRTSSIQPSFRHRSDDPVGSLWGENDYPEGIEMAS
  MEMANSYGHSLPGAPGSGYVNPAYVGESGPVHAYGNPPLSECDWHKSPQGQKLIASLIPM
  TSRDRIKAIRNQPRTMEEKRNLRKIVDKEKSKQTHRILQLNCCIQCLNSISRAYRRSKNS
  LSEILNSISLWQKTLKIIGGKFGTSVLSYFNFLRWLLKFNIFSFILNFSFIIIPQFTVAK
  KNTLQFTGLEFFTGVGYFRDTVMYYGFYTNSTIQHGNSGASYNMQLAYIFTIGACLTTCF
  FSLLFSMAKYFRNNFINPHIYSGGITKLIFCWDFTVTHEKAVKLKQKNLSTEIRENLSEL
  RQENSKLTFNQLLTRFSAYMVAWVVSTGVAIACCAAVYYLAEYNLEFLKTHSNPGAVLLL
  PFVVSCINLAVPCIYSMFRLVERYEMPRHEVYVLLIRNIFLKISIIGILCYYWLNTVALS
  GEECWETLIGQDIYRLLLMDFVFSLVNSFLGEFLRRIIGMQLITSLGLQEFDIARNVLEL
  IYAQTLVWIGIFFCPLLPFIQMIMLFIMFYSKNISLMMNFQPPSKAWRASQMMTFFIFLL
  FFPSFTGVLCTLAITIWRLKPSADCGPFRGLPLFIHSIYSWIDTLSTRPGYLWVVWIYRN
  LIGSVHFFFILTLIVLIITYLYWQITEGRKIMIRLLHEQIINEGKDKMFLIEKLIKLQDM
  EKKANPSSLVLERREVEQQGFLHLGEHDGSLDLRSRRSVQEGNPRA
• Function: Probable ion channel.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[1]
Prostate cancer	DISF190Y	Strong	Altered Expression	[2]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[2]
Lung adenocarcinoma	DISD51WR	Disputed	Altered Expression	[3]
Squamous cell carcinoma	DISQVIFL	Disputed	Biomarker	[3]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	Transmembrane channel-like protein 5 (TMC5) decreases the response to substance of Arsenic trioxide.	[15]

10 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Transmembrane channel-like protein 5 (TMC5).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Transmembrane channel-like protein 5 (TMC5).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Transmembrane channel-like protein 5 (TMC5).	[6]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Transmembrane channel-like protein 5 (TMC5).	[7]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Transmembrane channel-like protein 5 (TMC5).	[8]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Transmembrane channel-like protein 5 (TMC5).	[7]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Transmembrane channel-like protein 5 (TMC5).	[9]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Transmembrane channel-like protein 5 (TMC5).	[12]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Transmembrane channel-like protein 5 (TMC5).	[13]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Transmembrane channel-like protein 5 (TMC5).	[14]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Transmembrane channel-like protein 5 (TMC5).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Transmembrane channel-like protein 5 (TMC5).	[11]

References

• [1] Family-based association analyses of imputed genotypes reveal genome-wide significant association of Alzheimer's disease with OSBPL6, PTPRG, and PDCL3.Mol Psychiatry. 2016 Nov;21(11):1608-1612. doi: 10.1038/mp.2015.218. Epub 2016 Feb 2.
• [2] Transmembrane Channel-Like 5 (TMC5) promotes prostate cancer cell proliferation through cell cycle regulation.Biochimie. 2019 Oct;165:115-122. doi: 10.1016/j.biochi.2019.07.017. Epub 2019 Jul 26.
• [3] Eight potential biomarkers for distinguishing between lung adenocarcinoma and squamous cell carcinoma.Oncotarget. 2017 May 3;8(42):71759-71771. doi: 10.18632/oncotarget.17606. eCollection 2017 Sep 22.
• [4] Design principles of concentration-dependent transcriptome deviations in drug-exposed differentiating stem cells. Chem Res Toxicol. 2014 Mar 17;27(3):408-20.
• [5] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [8] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [9] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [10] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [11] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [12] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [13] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [14] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
• [15] The NRF2-mediated oxidative stress response pathway is associated with tumor cell resistance to arsenic trioxide across the NCI-60 panel. BMC Med Genomics. 2010 Aug 13;3:37. doi: 10.1186/1755-8794-3-37.